JP6062962B2 - 置換ピリミジン化合物およびｓｙｋ阻害剤としてのそれらの使用 - Google Patents

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Publication number

JP6062962B2

JP6062962B2 JP2014553451A JP2014553451A JP6062962B2 JP 6062962 B2 JP6062962 B2 JP 6062962B2 JP 2014553451 A JP2014553451 A JP 2014553451A JP 2014553451 A JP2014553451 A JP 2014553451A JP 6062962 B2 JP6062962 B2 JP 6062962B2

Authority

JP

Japan

Prior art keywords

methyl

ylamino

pyrazol

pyrimidin

indol

Prior art date

2012-01-20

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 239000003112 inhibitor Substances 0.000 title description 15
• 150000003230 pyrimidines Chemical class 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 284
• -1 trifluoromethylcarbonyl Chemical group 0.000 claims description 103
• 125000003118 aryl group Chemical group 0.000 claims description 72
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 59
• 150000003839 salts Chemical class 0.000 claims description 38
• 229920006395 saturated elastomer Polymers 0.000 claims description 38
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• 125000002950 monocyclic group Chemical group 0.000 claims description 35
• 125000005842 heteroatom Chemical group 0.000 claims description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
• 210000004027 cell Anatomy 0.000 claims description 24
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 208000006673 asthma Diseases 0.000 claims description 19
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
• JCZPOYAMKJFOLA-ZXZARUISSA-N (3s,4r)-pyrrolidine-3,4-diol Chemical compound O[C@H]1CNC[C@H]1O JCZPOYAMKJFOLA-ZXZARUISSA-N 0.000 claims description 18
• 125000000217 alkyl group Chemical group 0.000 claims description 16
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• 239000001301 oxygen Substances 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
• 239000011593 sulfur Substances 0.000 claims description 13
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 12
• 150000003457 sulfones Chemical group 0.000 claims description 11
• 206010025323 Lymphomas Diseases 0.000 claims description 10
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
• 150000003462 sulfoxides Chemical group 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 230000003325 follicular Effects 0.000 claims description 5
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
• LVDAOOBTKGLDAK-UHFFFAOYSA-N 1-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC(O)C1 LVDAOOBTKGLDAK-UHFFFAOYSA-N 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• QTNLJTSGFKCIKB-UHFFFAOYSA-N cyclopropyl-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1,2-dimethylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=C(C)N(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 QTNLJTSGFKCIKB-UHFFFAOYSA-N 0.000 claims description 4
• JSFJBYKBNANORA-OAQYLSRUSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypiperidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CCC[C@@H](O)C1 JSFJBYKBNANORA-OAQYLSRUSA-N 0.000 claims description 4
• FNGJTJGYKVSXHA-HXUWFJFHSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 FNGJTJGYKVSXHA-HXUWFJFHSA-N 0.000 claims description 4
• ZRYVEASTNWHZKR-ZRZAMGCNSA-N cyclopropyl-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1,2-dimethylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=C(C)N(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 ZRYVEASTNWHZKR-ZRZAMGCNSA-N 0.000 claims description 4
• 238000007918 intramuscular administration Methods 0.000 claims description 4
• 206010025135 lupus erythematosus Diseases 0.000 claims description 4
• BDZYVSQZYKURPZ-RBUKOAKNSA-N (3r,5s)-5-(hydroxymethyl)-1-[[3-methyl-1-[2-[(1-methyl-3-methylsulfonylindol-5-yl)amino]pyrimidin-4-yl]pyrazol-4-yl]methyl]pyrrolidin-3-ol Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(=CN(C)C4=CC=3)S(C)(=O)=O)N=CC=2)C=C1CN1C[C@H](O)C[C@H]1CO BDZYVSQZYKURPZ-RBUKOAKNSA-N 0.000 claims description 3
• GYPNQERNJVTKMG-HXUWFJFHSA-N 1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-dimethylpropan-1-one Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(C)(C)C)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 GYPNQERNJVTKMG-HXUWFJFHSA-N 0.000 claims description 3
• FLGSFJVMDOPSIH-GOSISDBHSA-N 1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CNC2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC[C@@H](O)C1 FLGSFJVMDOPSIH-GOSISDBHSA-N 0.000 claims description 3
• BOAWZTDHVMBMEN-KDURUIRLSA-N 1-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]-2,2,2-trifluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 BOAWZTDHVMBMEN-KDURUIRLSA-N 0.000 claims description 3
• RBKBIFWYNLXUJN-KDURUIRLSA-N 1-[5-[[4-[4-[[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]-2,2-difluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 RBKBIFWYNLXUJN-KDURUIRLSA-N 0.000 claims description 3
• LHGNCEUWLNJOPN-ZRZAMGCNSA-N 1-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-dimethylpropan-1-one Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(C)(C)C)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 LHGNCEUWLNJOPN-ZRZAMGCNSA-N 0.000 claims description 3
• WXWUQOPWCPNTJP-ZRZAMGCNSA-N 1-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1=C2C(C(=O)C(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1C[C@H](O)[C@H](O)C1 WXWUQOPWCPNTJP-ZRZAMGCNSA-N 0.000 claims description 3
• NQRYGQAPAJNGLL-OYRHEFFESA-N 1-[5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CNC2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1C[C@H](O)[C@H](O)C1 NQRYGQAPAJNGLL-OYRHEFFESA-N 0.000 claims description 3
• KBAODVSDRBXPFB-BJKOFHAPSA-N 1-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C(C)C)=CN(C)C4=CC=3)N=CC=2)N=C1C KBAODVSDRBXPFB-BJKOFHAPSA-N 0.000 claims description 3
• MUGXJGHVJPIMFQ-PMACEKPBSA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-difluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 MUGXJGHVJPIMFQ-PMACEKPBSA-N 0.000 claims description 3
• LHGNCEUWLNJOPN-GOTSBHOMSA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-dimethylpropan-1-one Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(C)(C)C)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 LHGNCEUWLNJOPN-GOTSBHOMSA-N 0.000 claims description 3
• WXWUQOPWCPNTJP-GOTSBHOMSA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1=C2C(C(=O)C(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1C[C@H](O)[C@@H](O)C1 WXWUQOPWCPNTJP-GOTSBHOMSA-N 0.000 claims description 3
• RBKBIFWYNLXUJN-OALUTQOASA-N 1-[5-[[4-[4-[[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]-2,2-difluoroethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)[C@@H](O)C1 RBKBIFWYNLXUJN-OALUTQOASA-N 0.000 claims description 3
• SWRICVFADHWLJK-UHFFFAOYSA-N 1-[[3-methyl-1-[2-[(1-methyl-3-pyrrolidin-1-ylsulfonylindol-5-yl)amino]pyrimidin-4-yl]pyrazol-4-yl]methyl]azetidin-3-ol Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(=CN(C)C4=CC=3)S(=O)(=O)N3CCCC3)N=CC=2)C=C1CN1CC(O)C1 SWRICVFADHWLJK-UHFFFAOYSA-N 0.000 claims description 3
• BVJHIQCBENLSSV-UHFFFAOYSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC(O)C1 BVJHIQCBENLSSV-UHFFFAOYSA-N 0.000 claims description 3
• ADWAHBOJNVCGRU-UHFFFAOYSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-2,3-dihydroindol-1-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4CCN(C4=CC=3)C(=O)C(F)(F)F)N=CC=2)C=C1CN1CC(O)C1 ADWAHBOJNVCGRU-UHFFFAOYSA-N 0.000 claims description 3
• QMUBTSPFECNPLS-ZWKOTPCHSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(2s,4r)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1C[C@H](O)C[C@H]1CO QMUBTSPFECNPLS-ZWKOTPCHSA-N 0.000 claims description 3
• HNWPDSDZWHSCID-DLBZAZTESA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(2s,4r)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1C[C@H](O)C[C@H]1CO HNWPDSDZWHSCID-DLBZAZTESA-N 0.000 claims description 3
• PQBYPDZGIKKGIO-MRXNPFEDSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 PQBYPDZGIKKGIO-MRXNPFEDSA-N 0.000 claims description 3
• ZRDGIOZDUKGYCA-QGZVFWFLSA-N 2,2-difluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 ZRDGIOZDUKGYCA-QGZVFWFLSA-N 0.000 claims description 3
• UGQOCPKHBJZKAA-MRXNPFEDSA-N 2,2-difluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 UGQOCPKHBJZKAA-MRXNPFEDSA-N 0.000 claims description 3
• FFPFVVNGWCWOPW-LEWJYISDSA-N 2,2-difluoro-1-[5-[[4-[4-[[(3s,4r)-3-hydroxy-4-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]ethanone Chemical compound C1[C@H](O)[C@H](OC)CN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C(F)F)=CN(C)C4=CC=3)N=CC=2)N=C1C FFPFVVNGWCWOPW-LEWJYISDSA-N 0.000 claims description 3
• VNVRFKHKLIDRLN-UHFFFAOYSA-N 5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-n,n,1-trimethylindole-3-carboxamide Chemical compound C1=C2C(C(=O)N(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC(O)C1 VNVRFKHKLIDRLN-UHFFFAOYSA-N 0.000 claims description 3
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 3
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
• KQVUHDMIGFMKFO-UHFFFAOYSA-N [1-[2-[(1-cyclopropyl-3-methylindol-5-yl)amino]pyrimidin-4-yl]-3-methylpyrazol-4-yl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C)=CN(C4=CC=3)C3CC3)N=CC=2)C=C1C(=O)N1CC(O)C1 KQVUHDMIGFMKFO-UHFFFAOYSA-N 0.000 claims description 3
• VLSXAYNYBJKZAV-JOCHJYFZSA-N cyclopropyl-[1-cyclopropyl-5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C4=CC=3)C3CC3)N=CC=2)C=C1CN1CC[C@@H](O)C1 VLSXAYNYBJKZAV-JOCHJYFZSA-N 0.000 claims description 3
• AAJLSZLYZUDYIH-HSZRJFAPSA-N cyclopropyl-[1-cyclopropyl-5-[[4-[4-[[(3r)-3-methoxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-3-yl]methanone Chemical compound C1[C@H](OC)CCN1CC1=CN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C4=CC=3)C3CC3)N=CC=2)N=C1C AAJLSZLYZUDYIH-HSZRJFAPSA-N 0.000 claims description 3
• WPXHOAVIWQSSDK-PLQXJYEYSA-N cyclopropyl-[1-cyclopropyl-5-[[4-[4-[[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C4=CC=3)C3CC3)N=CC=2)C=C1CN1C[C@H](O)[C@H](O)C1 WPXHOAVIWQSSDK-PLQXJYEYSA-N 0.000 claims description 3
• AROPBXPDYKPBNJ-UHFFFAOYSA-N cyclopropyl-[5-[[4-[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]indol-1-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C=CN(C4=CC=3)C(=O)C3CC3)N=CC=2)C=C1CN1CC(O)C1 AROPBXPDYKPBNJ-UHFFFAOYSA-N 0.000 claims description 3
• VUAQDGAQHZEJRI-LJQANCHMSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 VUAQDGAQHZEJRI-LJQANCHMSA-N 0.000 claims description 3
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